Dehydroacetic acid dental compositions



y 1956 H. M. BAUM DEHYDROACETIC ACID DENTAL COMPOSITIONS 2 Sheets-Sheet 1 Filed March 31, 1952 I I I I MOE @MFDZIL 3: v n M Q 8v [om I S I 3 1 Q o IQ 31v w N o mmmw u o mv 3 I l 1 I Q om A Q 1 I l l 0o 3 I $6 3 l IQN l ON I 2 m I1 May 22, 1956 H M. BAUM DEHYDROACETIC ACID DENTAL COMPOSITIONS 2 Sheets-Sheet 2 Filed March 31, 1952 III' I III QOE WMIDZZZ O.

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WWFDZZZ llllll'l QUE DEHYDRQACETEC ACID DENTAL COWOSITEQNS Harold M. Baum, Ladue, Mo., assignor to Warner-Lamhart Pharmaceutical Company, a corporation of Delaware Application March 31, 1952, Serial No. 279,648

9 Claims. (Cl. 167-93) This invention relates to therapeutic compositions and more particularly to therapeutic compositions for use in the oral cavity.

Briefly, the present invention is directed to dental therapeutic compositions which contain dehydroacetic acid compounds and which may also contain a water-soluble oxalate.

Among the several objects of the invention may be noted the provision of therapeutic compositions for use in the oral cavity which inhibit acid production for prolonged periods of time and are sufliciently persistent to inhibit acid formation from sugars ingested any time over a period of at least twelve hours; the provision of such therapeutic compositions which reduce the incidence of dental caries and which protect and whiten tooth enamel; the provision of compositions of the class described which increase the surface oxalate content of teeth and render teeth more resistant to acid attack; the provision of dental therapeutic compositions which are nontoxic, nonsensitizing, nonirritating and stable; and the provision of such therapeutic compositions which may be made from inexpensive and readily obtainable materials. Other features will be in part apparent and in part pointed out hereinafter.

The invention accordingly comprises the products hereinafter described, the scope of the invention being indicated in the following claims.

The accompanying drawings graphically illustrate the results of in vivo tests of the therapeutic activity and the inhibition of acid formation resulting from the use of the dental therapeutic compositions of the present invention, which tests will be described in detail hereinafter.

Research and study of dental caries etiology has revealed that tooth decay is the result of acid action on tooth enamel. It is also recognized that inorganic tooth enamel material will be dissolved at a pH of approximately 5.2 or below. Acids which will act to damage the teeth are produced by acidogenic bacterial action. These bacteria, the enzymes formed by such bacteria and a carbohydrate substrate are necessary elements in the chemical conversion of sugars or starches into these destructive acids.

It has been found in accordance with the present invention that the incidence of dental caries can be greatly reduced by the use of therapeutic compositions including dehydroacetic acid compounds. The introduction of such novel therapeutic compositions into the oral cavity inhibits acid formation over prolonged periods of time and operates to maintain the pH above a value of approximately 5.2. It has also been found that it is advantageous to incorporate a Water-soluble oxalate in the dehydroacetic acid compound-containing therapeutic compositions. Although the exact mechanism is'not entirely clear, it is believed that the dehydroacetic acid compound component of these therapeutic compositions inhibits acid production by inhibiting enzymatic action necessary in the conversion of carbohydrates to acids, while the water-soluble oxalate component operates as an enamel protective agent to in- 2,745,905 Patented May 22, 1956 crease the resistance of the tooth to acid attack. These therapeutic compositions will exert a sufiiciently persistent effect in inhibiting acid production to be elfective under conditions of morning and evening use. The dehydroacetic acid compounds specified herein are not only compatible with other components generally used in therapeutic compositions which may be used orally, but they are also stable, nontoxic, nonirritating, nonsensitizing, inexpensive and readily available. It is preferred, however, that these compositions do not include an aldehyde.

The therapeutic compositions of the present invention comprise a dehydroacetic acid compound and a vehicle for the compound which is compatible therewith. In the case of a dentifrice this vehicle would be the tooth cleaning components thereof. These compositions include not only paste, powder, and liquid dentifrices, but also mouthwashes, chewing gum, tablets, lozenges and troches. The percentage of the dehydroacetic acid compound incorporated in these therapeutic compositions may be varied considerably, although the preferred percentage by Weight is between approximately 0.5% and approximately 1.5%. The amount of oxalate component, if one is included in these compositions, similarly may be varied considerably, but a range of approximately 0.25% to approximately 1.5% by weight is preferred. These percentages may also vary depending upon whether the composition is a dentifrice, where say 1.0% of a dehydroacetic acid compound and 0.5% of the oxalate compound may be preferred, or a mouthwash where perhaps 0.5% of a dehydroacetic acid compound and 0.25% of the oxalate component are preferred.

It will be understood that the term dehydroacetic acid compound includes dehydroacetic acid and its watersoluble salts, such as, for example, the sodium, potassium and ammonium salts. Similarly, any water-soluble oxalate such as sodium, potassium and ammonium oxalates and the urea salt of oxalic acid may be utilized in these dental therapeutic compositions.

The following examples illustrate the invention.

Example 1 A dentifrice composition was prepared from the following components:

Components: Percent by weight Calcium sulfate 35.70 Dicalcium phosphate 15.60 Detergent 3.00 Gum tragacanth 1.40 Sodium saccharin 0.175 Glycerin 19.90 Water 22.525 Flavor 1.2 Sodium salt of dehydroacetic acid 0.50

Example 2 A dentifrice composition as described in Example 1 was prepared, except that 0.75% of the sodium salt of dehydroacetic acid was employed. The percentage by weight of the water component was adjusted to compensate for the increased percentage of the sodium salt of dehydroacetic acid.

Example 3 A dentifrice composition as described in Example 1 was prepared, except that 1.00% of the sodium salt of dehydroacetic acid was employed. The percentage by Weight of the water component was adjusted to compensate for the increased percentage of the sodium salt of dehydroacetic acid. a

Example 4 A dentrifrice composition was prepared from the following components:

Components: Percent by weight Alumina hydrate 48.30 Titanium dioxide 1.00 Detergent 3.00 Gum tragacanth 0.56 Sodium saccharin 0.15 d-Sorbitol solution 19.10 Glycerin 12.80 Water 12.62 Flavor 1.22 Sodium salt of dehydroacetic acid 0.75 Sodium oxalate 0.50

Example 5 A dentrifrice composition was prepared from the following components:

Components: Percent by weight Alumina hydrate 48.30 Titanium dioxide 1.00 Detergent 3.00 Gum tragacanth 0.56 Sodium saccharin 0.15 d-Sorbitol solution 19.10 Glycerin 12.80 Water 12.37 Flavor 1.22 Sodium salt of dehydroacetic acid 1.00 Sodium oxalate 0.50

Example 6 A mouthwash was prepared from the following components:

Ethyl alcohol ml 12.00

Water q. s. to rn1 100.00

Sodium salt of dehydroacet'ic acid g 1.00

Example 7 A mouthwash was prepared from the following components:

Ethyl alcohol ml 12.00

Water q. s. to ml 100.00

Sodium salt of dehydroacetic acid g 0.75

Sodium oxalate g 0.25

Example 8 A number of subjects were given a standard dentrifrice which they used morning and evening for seven days. On the morning of the eighth day, and after the morning brushing, a 10 ml. sample of saliva, stimulated by chewing parafiin, was obtained from each subject. Duplicate samples of 4 ml. each were removed from the original 10 ml. sample and 1 ml. of glucose-water solution was added to each 4 ml. saliva sample. An initial pH of these (4 ml. saliva plus 1 ml. glucose solution) samples was determined by a Beckmann pH meter immediately after addition of the glucose solution. These two samples were incubated at 37.5 C. for four hours, the pH of each of the two samples being taken at two and at four hours after the initial pH determination. The averages of the pH values at O, 2 and 4 hours were plotted against time as shown by the dashed line of Fig. 1.

The same subjects were then each given a sample of the dentifrice of Example 1 which they used morning and evening for seven more days. On the morning of the eighth day, and without a morning brushing, a 10 ml. sample of stimulated saliva was taken, duplicate 4 ml. samples removed, glucose solution added, the samples incubated and the pH determined as described in the preceding paragraph. The results are indicated graph ically by the solid-line curve of Fig. 1,

4 Example 9 The procedure of Example 8 was repeated using the dentifrice of Example 2 in place of the Example 1 dentifrice.

The average pH values after the initial seven-day period are shown by the dashed-line curve of Fig. 2, and the results after the second seven-day period are shown by the solid-line curve of Fig. 2.

Example 10 A number of subjects were selected and the normal curve of the rate of acid production in the mouth was determined as follows: A given area of a given tooth of each subject was marked oft" and the pH of this tooth area was determined by means of microelectrode technique. The subjects then immediately rinsed their mouths for thirty seconds with a rinse of a 50% aqueous sucrose solution. The pH of the area was again determined by the microelectrode technique at intervals of 5, l0 and 15 minutes after the first pH determination. The averages of the pH values at 0, 5, 10, 15 and 20 minutes were plotted versus time as shown by the dashedline curve of Fig. 3.

The same subjects were then each given a supply of the dentrifrice of Example 2 which they used morning and evening for seven days. On the morning of the eighth day, and without a morning brushing, the pH of the marked tooth area of each subject was again determined by means of microelectrode technique. The subjects then immediately rinsed their months for thirty secends with a rinse of a 50% aqueous sucrose solution. The pH was again determined at intervals of 5, 10, 15 and 20 minutes after the first pH determination. The average pH values were plotted versus time as shown by the solid-line curve of Fig. 3.

Example 11 The procedure of Example 8 was repeated using the dentifrice of Example 3 in place of the Example 1 dentifrice. The average pH values of the control curve are shown by the dashed-line curve of Fig. 4, and the results after the seven-day test period are shown by the solidline curve of Fig. 4.

Example 12 The procedure of Example 10 was repeated using the dentrifn'ce of Example 3 in place of the Example 2 dentifrice.

The average pH values of the control curve are shown by the dashed-line curve of Fig. 5, and the results after the seven-day test period are shown by the solid-line curve of Fig. 5.

Example 13 The procedure of Example 10 was repeated using the dentifrice of Example 4 in place of the Example 2 dentifrice.

The average pH values of the control curve are shown by the dashed-line curve of Fig. 6, and the results after the seven-day test period are shown by the solid-line curve of Fig. 6.

Example 14 The procedure of Example 10 was repeated using the dentifrice of Example 5 in place of the Example 2 dentifrice.

The average pH values of the control curve are shown by the dashed-line curve of Fig. 7, and the results after the seven-day test period are shown by the solid-line curve of Fig. 7.

Example 15 The procedure of Example 10 was repeated using the mouthwash of Example 6 in place of the dentifrice of Example 2. It is to be understood that the mouthwash was used morning and evening as a mouth rinse instead of brushing the teeth morning and evening.

The average pH values of the control curve are shown by the dashed'line curve of Fig. 8, and the results after the seven-day test period are shown by the solid-line curve of Fig. 8.

Example 16 The procedure of Example was repeated using the mouthwash of Example 7 in place of the dentifrice of Example 2. it is to be understood that the mouthwash was used morning and evening as a mouth rinse instead or" brushing the teeth morning and evening.

The average pH values of the control curve are shown by the dashed-line curve of Fig. 9, and the results after the seven-day test period are shown by the solid-line curve of Fig. 9.

in view of the above, it will be seen that the several objects of the invention are achieved and other advantageous results attained.

As many changes could be made in the above products without departing from the scope of the invention, it is intended that all matter contained in the above description or shown in the accompanying drawings shall be interpreted as illustrative and not in a limiting sense.

1 claim:

1. A therapeutic mouthwash comprising not less than 0.5 by weight of a compound selected from the group consisting of dehydroacetic acid and the water soluble salts of dehydroacetic acid and a dispersing vehicle compatible with said compound.

2. A dental therapeutic composition comprising not less than 0.5 by weight of a compound selected from the group consisting of dehydroacetic acid and the water soluble salts of dehydroacetic acid, and a dispersing vehicle compatible with said compound.

3. A dental therapeutic composition comprising not substantially less than 0.5% by weight of a compound selected from the group consisting of dehydroacetic acid and the water soluble salts of dehydroacetic acid, not substantially less than 0.25% by weight of a water-soluble oxalate, and a vehicle for said compound and oxalate, said vehicle being compatible with said compound.

4. A therapeutic dentifrice comprising not substantially less than 0.5% by weight of a compound selected from the group consisting of dehydroacetic acid and the water soluble salts of dehydroacetic acid, not substantially less than 0.25 by Weight of a Water-soluble oxalate, and tooth cleaning components, said tooth cleaning components being compatible with said compound.

5. A therapeutic mouthwash comprising not substantially less than 0.5% by weight of a compound selected from the group consisting of dehydroacetic acid and the Water soluble salts of dehydroacetic acid, not substantially less than 0.25% by weight of a water-soluble oxalate, and a vehicle for said compound and oxalate, said vehicle being compatible with said compound.

6. A therapeutic dentifrice comprising approximately 0.7 5% by weight of a compound selected from the group consisting of dehydroacetic acid and the water soluble salts of dehydroacetic acid, approximately 0.5% by weight of a water-soluble oxalate, and tooth cleaning components, said tooth cleaning components being compatible with compound.

7. A therapeutic mouthwash comprising approximately 0.5% by weight of a compound selected from the group consisting of dehydroacetic acid and the water soluble salts of dehydroacetic acid, approximately 0.25 by weight of a water-soluble oxalate, and a vehicle for said compound and oxalate, said vehicle being compatible with acid compound.

8. A therapeutic paste dentifrice comprising approximately 0.75% by Weight of the sodium salt of dehydroacetic acid, approximately 0.5% by weight of sodium oxalate, and tooth cleaning components, said tooth cleaning components being compatible with said salt.

9. A therapeutic mouthwash comprising approximately 0.5% by weight of the sodium salt of dehydroacetic acid, approximately 0.25 by weight of sodium oxalate, and an alcohol-water vehicle.

References Cited in the file of this patent UNITED STATES PATENTS 2,474,227 Coleman et a1 June 28, 1949 2,474,229 Coleman June 28, 1949 FOREIGN PATENTS 134, 156 Australia Sept. 6, 1947 OTHER REFERENCES Orol Surgery, Oral Med. and Oral Path, April 1949,

Oral Medicine, pages 459-473 (page 471 pertinent).

Science News Letter, August 29, 1953, page 131. Goodman: Cosmetic Dermatology, McGraw-Hill Book' Company, Inc., page 424 (1936).

Science News Letter, page 252, October 18, 1947. 

1. A THERAPEUTIC MOUTHWASH COMPRISING NOT LESS THAN 0.5% BY WEIGHT OF A COMPOUND SELECTED FROM THE GROUP CONSISTING OF DEHYDROACETIC ACID AND THE WATER SOLUBLE SALTS OF DEHYDROACETIC ACID AND DISPERSING VEHICLE COMPATIBLE WITH SAID COMPOUND. 